Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
Nat Neurosci. 2022 May;25(5):596-606. doi: 10.1038/s41593-022-01052-2. Epub 2022 May 2.
Activity-dependent myelination can fine-tune neural network dynamics. Conversely, aberrant neuronal activity, as occurs in disorders of recurrent seizures (epilepsy), could promote maladaptive myelination, contributing to pathogenesis. In this study, we tested the hypothesis that activity-dependent myelination resulting from absence seizures, which manifest as frequent behavioral arrests with generalized electroencephalography (EEG) spike-wave discharges, promote thalamocortical network hypersynchrony and contribute to epilepsy progression. We found increased oligodendrogenesis and myelination specifically within the seizure network in two models of generalized epilepsy with absence seizures (Wag/Rij rats and Scn8a mice), evident only after epilepsy onset. Aberrant myelination was prevented by pharmacological seizure inhibition in Wag/Rij rats. Blocking activity-dependent myelination decreased seizure burden over time and reduced ictal synchrony as assessed by EEG coherence. These findings indicate that activity-dependent myelination driven by absence seizures contributes to epilepsy progression; maladaptive myelination may be pathogenic in some forms of epilepsy and other neurological diseases.
活动依赖性髓鞘形成可以精细调节神经网络的动力学。相反，异常的神经元活动，如反复发作性癫痫（癫痫）中发生的活动，可能会促进适应性髓鞘形成，从而促进发病机制。在这项研究中，我们测试了以下假设：由癫痫发作引起的活动依赖性髓鞘形成会促进丘脑皮质网络过度同步，并导致癫痫进展。我们发现，在两种具有癫痫发作的全身性癫痫模型（Wag/Rij 大鼠和 Scn8a 小鼠）中，仅在癫痫发作后，癫痫发作网络中出现了明显的少突胶质细胞生成和髓鞘形成增加。Wag/Rij 大鼠中的药物性癫痫抑制可预防异常髓鞘形成。阻断活动依赖性髓鞘形成可随时间减少癫痫发作负担，并降低脑电图相干性评估的发作同步性。这些发现表明，由癫痫发作驱动的活动依赖性髓鞘形成会导致癫痫进展；适应性髓鞘形成可能在某些形式的癫痫和其他神经疾病中具有致病性。
